Project Summary: Maintaining healthy physiology of the human gut is a large focus of Pharma. Models to study drug/nutrient absorption, xenobiotics, toxicology, and preclinical efficacies are hampered by the lack of accurate, reproducible, and easy to use cell culture models to evaluate such topics. For these reasons, there is a strong need for better in vitro models that recapitulate disease states of the human gut, and better platforms for drug discovery and validation. To meet this need Altis Biosystems Inc., an early stage biotechnology company, will collaborate with scientists at the University of North Carolina at Chapel Hill to develop novel, rapidly screenable cells that can be generated on, and applied to, their gut stem cell-based technology called RepliGut?, which is a monolayer of human epithelium derived the small intestine or colon of organ donors, and contains all of the proliferative and differentiated cell types found in vivo. This Phase I study will 1) develop and optimize novel methods to for generating robust fluorescent protein based cell lines by transgenesis or CRISPR-gene editing, 2) create and validate two screenable cell lines to report key properties associated with gut health and disease - epithelial barrier function and inflammation, and 3) perform a proof-of-concept small scale compound screen to demonstrate utility and provide rationale for expanded development. These screenable cells will be developed with the eventual goal during Phase II of creating screenable cells and genetic disease model on RepliGut? that can fit into high-throughput and high-content screening infrastructure. This collaboration between academia, Altis, and the NIH represents an ideal opportunity to further develop RepliGut? for translation of this highly physiologic culture and screening platform into an underdeveloped marketplace.